Mechanism of tryptanthrin in treatment of ulcerative colitis in mice based on serum metabolomics / 中国中药杂志

This study aims to explore the effect of tryptanthrin on potential metabolic biomarkers in the serum of mice with ulcerative colitis(UC) induced by dextran sulfate sodium(DSS) based on liquid chromatography-mass spectrometry(LC-MS) and predict the related metabolic pathways. C57BL/6 mice were randomly assigned into a tryptanthrin group, a sulfasalazine group, a control group, and a model group. The mouse model of UC was established by free drinking of 3% DSS solution for 11 days, and corresponding drugs were adminsitrated at the same time. The signs of mice were observed and the disease activity index(DAI) score was recorded from the first day. Colon tissue samples were collected after the experiment and observed by hematoxylin-eosin(HE) staining. The levels of interleukin-4(IL-4), interleukin-10(IL-10), tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), and interleukin-8(IL-8) in the serum were measured by enzyme linked immunosorbent assay(ELISA). The serum samples were collected from 6 mice in each group for widely targeted metabolomics. The metabolic pathways were enriched by MetaboAnalyst 5.0. The results showed that compared with the model group, tryptanthrin treatment decreased the DAI score(P<0.05), alleviated the injury of the colon tissue and the infiltration of inflammatory cells, lowered the levels of proinflammatory cytokines, and elevated the levels of anti-inflammatory cytokines in the serum. The metabolomic analysis revealed 28 differential metabolites which were involved in 3 metabolic pathways including purine metabolism, arachidonic acid metabolism, and tryptophan metabolism. Tryptanthrin may restore the metabolism of the mice with UC induced by DSS to the normal level by regulating the purine metabolism, arachidonic acid metabolism, and tryptophan metabolism. This study employed metabolomics to analyze the mechanism of tryptanthrin in the treatment of UC, providing an experimental basis for the utilization and development of tryptanthrin.

Advances of monogenic kidney stone diseases associated with purine metabolism / 中华泌尿外科杂志

Some kidney stones are caused by single gene mutations, and monogenic kidney stone diseases associated with purine metabolic disorder mainly including adenine phosphoribosyltransferase(APRT) deficiency, hypoxanthine-guanine phosphoribosyltransferase(HPRT)deficiency, hereditary xanthinuria(HX), and some diseases caused by gene mutations such as PRS1, SLC22A12, SLC2A9 and ABCG2. Such diseases can lead to abnormal metabolism of purine and uric acid, and then form 2, 8-dihydroxyadenine stones, uric acid stones or xanthine stones. This kind of diseases are rare, the genotype and phenotype of different types of monogenic diseases related to purine metabolism have their own characteristics and are not widely recognized. At present, the main treatment is medical therapy. Gene sequencing will make the diagnosis and find more disease-related genes or mutations. Gene editing, such as CRISPR/Cas9 technology, makes it possible to cure monogenic kidney stone diseases associated with purine metabolism disorder in the future.

Advances in the pathogenesis of depression based on purinergic system and purine metabolism / 药学学报

Depression was a complex and difficult to regulate disease, which was closely related to purinergic system and purine metabolism disorder. Although there had been studies to improve depression by regulating purinergic system, the mechanism of action was complex and needed to be sorted out. Recently, a large number of studies had found that the addition of exogenous purine metabolites adenosine, inosine and guanosine had a significant antidepressant effect, indicating that regulating the level of purine substances in purine metabolism could also improve depression, which was of great significance to the further study of the pathogenesis and treatment of depression. In view of this, this study reviewed the relationship between purinergic system or purine metabolism and depression, in order to provide a reference for the further study of the pathogenesis of depression.

Material Basis and Mechanism of Kaixinsan for Treatment of Alzheimer's Disease Based on Integrated Pharmacological Platform of Chinese Medicine / 中国实验方剂学杂志

Objective: To explore the interrelation of "composition-target-disease" of Kaixinsan on treatment of Alzheimer's disease. Method: Through the integrated pharmacological platform of Chinese medicine V1.0,the active ingredients and potential targets of four Chinese herbs in Kaixinsan were collected,disease targets of Alzheimer's disease were searched,and enriched by the gene ontology database and the Kyoto encyclopedia of genes and genomes at hubs. Result: Among the 250 compounds of Kaixinsan,2 877 targets were associated with Alzheimer's disease.The key targets,such as mitochondrial trifunctional enzyme subunit alpha(HADHA),hydroxyacyl coenzyme A dehydrogenase(HADH),sterol-4-alpha-carboxylate 3-dehydrogenase(NSDHL) and others,played their pharmacological effects mainly through regulating purine and nucleotide metabolism,Huntington's disease,Alzheimer's disease,neurodegenerative diseases,oxidative phosphorylation,and endocrine and metabolic diseases in molecular reactions,such as cytoplasm,mitochondria,adenosine triphosphate binding,and mitochondrial matrix. Conclusion: The platform can predict the key targets and related pathways of Kaixinsan for treatment of Alzheimer's disease,which lays the foundation for further revealing material basis and mechanism of this formula,and plays an important role in digging and developing this classic and famous formula.

Pharmacological research progress of myocardial ischemia based on the metabonomics / 中国药学杂志

Cardiac hypo-function caused by myocardial ischemia is considered as the first killer of human health. The related metabolites in body can be changed due to the lack of blood and oxygen. These metabolites generated by pathological and physiology changes or exogenous intervention are extreme complicated, and the existing test methods can't satisfy the prospected purpose due to the lower sensitivity, more narrow liner range and so on. Therefore, the concept of metabonomics, a systemic analysis method, was put forward. Metabolites can be quantified in temporal and spatial dimension by metabonomics featured in a high throughput, higher detective sensitivity and wider liner range manner. So it has gradually been applied to many areas including myocardial ischemia. In this paper, based on the comprehensive research literature in domestic and overseas in recent years, the application of metabonomics in pharmacological research of myocardial ischemia was summarized. Five kinds of metabolic pathways are related with myocardial ischemia including sugar metabolism, energy metabolism, amino acid metabolism, purine metabolism and soluble epoxide hydrolase table oxidase P450 metabolism. Some drugs can be used to myocardial ischemia via these pathways. These representative drugs and their mechanisms which are analyzed by metabonomics were concluded in this paper.